CN103054851A - Application of chloranthalactone C in preparation of anti-tumor medicament - Google Patents
Application of chloranthalactone C in preparation of anti-tumor medicament Download PDFInfo
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- CN103054851A CN103054851A CN2011103265195A CN201110326519A CN103054851A CN 103054851 A CN103054851 A CN 103054851A CN 2011103265195 A CN2011103265195 A CN 2011103265195A CN 201110326519 A CN201110326519 A CN 201110326519A CN 103054851 A CN103054851 A CN 103054851A
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Abstract
The invention belongs to the fields of chemical industry and medicine, and relates to application of chloranthalactone C in preparation of an anti-tumor medicament. The chloranthalactone C is a natural product, and belongs to a sesquiterpenoid compound. The sesquiterpenoid compound is distributed in whole chloranthaceae plant, and has the bioactivities of diminishing inflammation, relieving spasm, inhibiting microbes and the like. The chloranthalactone C and derivatives thereof extracted from fresh roots have an antifungal effect. Experiments show that the chloranthalactone C can obviously inhibit proliferation of tumor cells. According to the invention, the tumor can be liver cancer, leukemia, cervical cancer, breast cancer or pancreatic cancer. The chloranthalactone C can be used as a new anti-tumor medicament or an auxiliary component thereof and developed, has an obvious tumor inhibiting effect, is environment-friendly, and provides a new path and means for treating and healing tumors.
Description
Technical field
The invention belongs to chemical field and field of medicaments, relate to the application of chloranthalactone C in the preparation antitumor drug.
Background technology
Herba chloranthi japonici typically refers to herb or the root and rhizome of Chloranthaceae plant Herba chloranthi japonici (Chloranthus Japonicus Sieb).Sesquiterpenoids is a compounds important in the Chloranthaceae plant, in whole Chloranthaceae plant distribution is arranged all, has the biological activitys such as antiinflammatory spasmolytic, inhibition microorganism.Obtain half its skeleton of terpenoid complex structure in the Herba chloranthi japonici and can be divided into a few types such as eudesmane type, ring eudesmane-type, germacrane, acorane type, they have the various ways such as lactone, ketone, alcohol, polymer simultaneously.
Studies show that, Jin Lilannei vinegar A, the moderate cytotoxic activity of B tool (Uchida M, Koike Y, Kusano G, et al.Studies on the constituentsof Chloranthus spp.III.Six sesquiterpenes fromChloranthus japonicus[J] .Chem Pharm Bull, 1980,28 (1): 92-102).And Jin Lilan lactone C and the derivant thereof from fresh, told, then have antifungic action (such as the blue trichobacteria of ash) [Zhou Baiting. China's gold chestnut Cymbidium medicinal plants chemical constituent and Advance on Pharmacological Activities [J]. Chinese crude drug, 2004,27 (7): 539-542.].
Chloranthalactone c (chloranthalactone C), colourless prism-shaped crystallization, 159～160 ℃ of fusing points.Be dissolved in methanol and chloroform.Structure is as follows:
As far back as the eighties in last century, just from Herba chloranthi japonici (Chloranthus japonicus), separate and obtained chloranthalactone c (Tahara S, Fukushi Y, Kawabata J, et al.Lindenanolides inthe root of Chloranthus japonicus (Chloranthaceae) [J] .Agric Biol Chem, 1981,45 (6): 1511-1512.).In China, the king frightens long the grade and also adopts the multiple chromatographic column separation means such as silica gel, MCI and RP-18, use the spectroscopic techniques such as NMR and MS, from silk fringe chu lan tree root, separate and identified sesquiterpenoid chloranthalactone C (WANG Xia-Chang, WU Wei-Qun, MA Shi-Ping, LIU Jing-Han, HU Li-Hong, A New Sesquiterpenoid from the Roots of Chloranthus fortunei, Chinese Journal of Natural Medicines 6 (2008) 0404-0407).
Chloranthalactone c belongs to natural product, and toxic and side effects is less, bioavailability is high, stable in properties, has clinical use value.Along with people to the going deep into of this type of alkaloidal chemistry and biology research, its molecular mechanism of action will progressively clear and definite, this will further promote chemical constitution modification and the structure activity study of this compounds, and help to improve the medical value of this compounds.But, the functional study of chloranthalactone c is waited deeply.
Summary of the invention
The new medicinal usage that the purpose of this invention is to provide chloranthalactone C.
The invention provides the application of chloranthalactone C in the preparation antitumor drug.Described antitumor drug is injection or tablet.Described antitumor drug can be medicines resistant to liver cancer or medicament for resisting cervical cancer.This antitumor drug can be injection or tablet.
The invention provides a kind of method that suppresses tumor cell in vitro propagation, chloranthalactone C is added in the culture fluid of tumor cell.Described tumor cell is hepatoma carcinoma cell or cervical cancer cell.The hepatoma carcinoma cell that adopts in one embodiment of the present of invention is SMMC-7721 and Hep G2.Generally speaking, the final concentration that adds chloranthalactone C is 10-500 μ M, 15-500 μ M for example, 16-500 μ M, 15-17 μ M etc.
The present invention also provides a kind of antitumor drug, and the active component of described antitumor drug is chloranthalactone C.Described tumor can be hepatocarcinoma or cervical cancer.
Micromolecular compound of the present invention can adopt the preparation method preparation of various routines.For example, adopt the synthetic method of artificial chemistry.
Utilize micromolecular compound of the present invention, by various conventional screening techniques, can filter out with chloranthalactone C interactional material occurs, such as receptor, inhibitor or antagonist etc.
The present invention and inhibitor, antagonist etc. when when (administration) used in treatment, can provide different effects.Usually, but these materials are formulated in nontoxic, inertia with pharmaceutically acceptable aqueous carrier medium in, wherein pH is about 5-8 usually, preferably pH is about 6-8, although pH value can change to some extent with the character that is formulated material and disease to be treated.The pharmaceutical composition for preparing can carry out administration by conventional route, comprising (but being not limited to): intramuscular, intraperitoneal, subcutaneous, Intradermal or topical.
Take chloranthalactone C of the present invention as example, can be with itself and suitable pharmaceutically acceptable carrier coupling.This class pharmaceutical composition contains chemical compound and pharmaceutically acceptable carrier or the excipient for the treatment of effective dose.This class carrier comprises (but being not limited to): saline, buffer, glucose, water, glycerol, ethanol and combination thereof.Pharmaceutical preparation should be complementary with administering mode.Chloranthalactone C of the present invention can be made into the injection form, for example is prepared by conventional method with normal saline or the aqueous solution that contains glucose and other adjuvant.Pharmaceutical composition such as Tablet and Capsula can be prepared by conventional method.Pharmaceutical composition such as injection, solution, Tablet and Capsula should be made under aseptic condition.The dosage of active component is the treatment effective dose, for example every day about 1 microgram/kg body weight-Yue 5 mg/kg body weight.In addition, chloranthalactone C of the present invention also can use with the other treatment agent.
When chloranthalactone C of the present invention is used as medicine, the chloranthalactone C for the treatment of effective dose can be applied to mammal, wherein should treat effective dose usually at least about 10 micrograms/kg body weight, and in most of the cases be no more than about 8 mg/kg body weight, preferably this dosage is about 10 micrograms/kg body weight-Yue 1 mg/kg body weight.Certainly, concrete dosage also should be considered the factors such as route of administration, patient health situation, and these all are within the skilled practitioners skill.
The invention provides the application of chloranthalactone C in the preparation antitumor drug.Chloranthalactone C is natural product, obviously the propagation of inhibition tumor cell.Micromolecular compound of the present invention is developed as new antitumor drug or its auxiliary element, and tumor killing effect is obvious, environmental protection, and will and cure tumor for treatment provides a kind of new approach and means.
The specific embodiment
Experimental technique:
1. cell recovery
1) from liquid nitrogen container, takes out cryopreservation tube, directly drop in 37 ℃ of warm water, and frequently shake and make it melt as early as possible.
2) take out cryopreservation tube from 37 ℃ of water-baths, with suction pipe sucking-off cell suspension, inject centrifuge tube and add culture fluid more than 10 times, low-speed centrifugal after mixing is abandoned supernatant, repeats to wash once with culture fluid again.
3) with after the suitable dilution of culture fluid, the inoculated and cultured bottle is placed on 37 ℃ of incubators and leaves standstill cultivation, changes culture fluid next day, continues to cultivate.Go down to posterity when being cultured to finite concentration.Cell culture contains 100U/ml penicillin and 100 μ g/ml streptomycins in the culture medium in containing the DMEM high glucose medium of 10% hyclone.
2. passage is cultivated
The situation of observation of cell growth every day goes down to posterity when converging when cell grows to about 90% in culture bottle, goes down to posterity once every 2-4 days approximately.One bottle goes down to posterity into three bottles, or a 25cm
2Go down to posterity in a 75cm
2Culture bottle in.Method:
1) with 1 * phosphate buffer washed cell once.
2) add the digestion of 2-3ml trypsinization liquid, place 37 ℃ of incubator numbers minute.Pat Tissue Culture Flask with hands, make cell separation.
3) suitable culture medium with the Gibico hyclone that contains 10-15% stops trypsinization.Cell is sub-packed in the new culture bottle, continues to cultivate.
3. cell cryopreservation
1) get the cell tryptase protease digestion that is cultured to exponential phase, be collected in the centrifuge tube and counting, centrifugal.
2) reject trypsin and old culture fluid add the frozen culture fluid (containing 10%DMSO, 40%DMEM and 50%Gibico hyclone) that configures, and the ultimate density of cell is 0.5-1 * 10 in the cryopreserving liquid
7/ ml.Blow and beat gently with suction pipe and to make cell even, then be distributed in the aseptic cryopreservation tube, every pipe adds 1-1.5ml.
3) cryopreservation tube is put into freezing storing box and put-80 ℃ of quick-freezings, move in the liquid nitrogen container after 5 hours and preserve.
Embodiment 1MTS method is measured chloranthalactone C to the growth inhibited effect of hepatoma carcinoma cell
SMMC-7721 cell (available from Chinese Academy of Sciences's cell bank) 1 * 10
3/ hole is seeded to 96 orifice plates, cultivates to make it adherent rear adding chloranthalactone C (available from Shanghai Pharmaceutical Inst., Chinese Academy of Sciences) in 24 hours, establishes 5 Concentraton gradient, and each concentration is established 3 multiple holes.Adding consistency is respectively 50,16.67,5.56,1.85,0.62 μ M.Cell is at 37 ℃, 5%CO
2Cultivate after 72 hours under the condition, outwell culture fluid, measure cell survival rate with MTS test kit (Promega company).
Method of testing is: cell is washed one time with serum-free medium, added the MTS chromophoric solution (adding 2ml solution 1 and 100 μ l solution 2 in the 10ml serum-free medium, fully mixings) for preparing in advance according to the amount of 100 μ l/well.Do not have the hole of cell to be made as this bottom outlet with one, absorb in order to the bias light of calibration solution.Cell is put into cell culture incubator to be continued to cultivate 2～4 hours, then read absorbance value (reference wavelength 630-700nm with microplate reader, measure wavelength 490nm), calculate cell survival rate, to measure hole absorbance value/control wells absorbance value as the numerical value of cell survival rate.According to cell survival rate, calculate chloranthalactone C to the IC50 value of SMMC-7721 cell.
IC50 refers to the concentration of a suppressed half inhibitor.Here be the SMMC-7721 cell quantity and be the concentration of a half chloranthalactone C of contrast.
The result: chloranthalactone C is 15.97 μ M to the IC50 value of SMMC-7721 cell.
Use the same method and test hep G2 cell (available from ATCC, American type culture collection, US mode culture collection warehousing), chloranthalactone C is about 16.98 μ M to the IC50 value of Hep G2 cell as a result.
Embodiment 2 chloranthalactone C are to the growth inhibited effect of human cervical carcinoma cell
Utilize cck-8 test kit (Japanese colleague's chemistry institute) to detect.
Step:
1) Hela cell (available from ATCC) is planted in 96 orifice plates uniformly, every porocyte number is 3000.
2) treat adherent, the rear dosing of spending the night, adding consistency is respectively 50,16.67,5.56,1.85,0.62 μ M, each concentration has 3 multiple holes.
3) cultivate 48 hours, complete medium is replaced to the mixture (10: 1) of serum-free medium and CCK8, hatched 2 hours in 37 ℃ of incubators.
4) take 450nm as measuring wavelength, take 650nm as the contrast wavelength, on microplate reader, measure reading.
The result: chloranthalactone C is about 497 μ M to the IC50 value of Hela cell.
Claims (10)
1. the application of chloranthalactone c in the preparation antitumor drug is characterized in that described tumor is hepatocarcinoma, leukemia, cervical cancer, breast carcinoma or cancer of pancreas.
2. application as claimed in claim 1 is characterized in that, described antitumor drug is medicines resistant to liver cancer.
3. application as claimed in claim 1 is characterized in that, described antitumor drug is medicament for resisting cervical cancer.
4. application as claimed in claim 1 is characterized in that, this antitumor drug is injection or tablet.
5. a method that suppresses tumor cell in vitro propagation is characterized in that, chloranthalactone c is added in the culture fluid of tumor cell.
6. method as claimed in claim 5 is characterized in that, described tumor cell is hepatoma carcinoma cell or cervical cancer cell.
7. method as claimed in claim 6 is characterized in that, described hepatoma carcinoma cell is SMMC-7721 or Hep G2.
8. method as claimed in claim 5 is characterized in that, the final concentration that adds chloranthalactone c is 10-500 μ M.
9. an antitumor drug is characterized in that, the active component of described antitumor drug is chloranthalactone c.
10. antitumor drug as claimed in claim 9 is characterized in that, described tumor is hepatocarcinoma or cervical cancer.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105646413A (en) * | 2016-03-01 | 2016-06-08 | 江西中医药大学 | Linderane compound capable of inhibiting microtubulin and preparation method and application of linderane compound capable of inhibiting microtubulin |
| CN108938865A (en) * | 2018-07-26 | 2018-12-07 | 广西壮族自治区药用植物园 | The preparation method for treating liver cancer, four monsoon tablet of nasopharyngeal carcinoma |
-
2011
- 2011-10-24 CN CN2011103265195A patent/CN103054851A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| MASAAKI UCHIDA,ET AL.: "Studies on the constituents of Chloranthus spp.III.Six sesquiterpenes from Chloranthus japonicus", 《CHEM.PHARM.BULL.》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105646413A (en) * | 2016-03-01 | 2016-06-08 | 江西中医药大学 | Linderane compound capable of inhibiting microtubulin and preparation method and application of linderane compound capable of inhibiting microtubulin |
| CN105646413B (en) * | 2016-03-01 | 2018-07-13 | 江西中医药大学 | A kind of lindera alkyl compound and its preparation method and application inhibiting tubulin |
| CN108938865A (en) * | 2018-07-26 | 2018-12-07 | 广西壮族自治区药用植物园 | The preparation method for treating liver cancer, four monsoon tablet of nasopharyngeal carcinoma |
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Application publication date: 20130424 |